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A novel water-soluble cyclosporine A prodrug: ocular tolerance and in vivo kinetics

Publié dansInternational journal of pharmaceutics, vol. 295, no. 1-2, p. 7-14
Date de publication2005
Résumé

The purpose of this study is to demonstrate that a novel water-soluble prodrug of cyclosporine A (CsA) intended for topical ocular administration, does not induce eye irritation in a rabbit model and is able to generate therapeutic concentrations of CsA in the precorneal area immediately after administration. The eye irritancy of the prodrug and CsA control solution was assessed by the Draize test and by confocal laser ophthalmoscopy (CLSO). Residence time and tear concentrations of prodrug and CsA in the rabbit eye were assessed by HPLC. The Draize test showed an excellent tolerance for the prodrug solution while the reference CsA oil solution induced lachrymation and irritation. The CLSO-measured corneal lesions, subsequent to treatment with the prodrug and reference solutions, were 3% and 9%, respectively. The prodrug transformed rapidly, leading to relatively stable CsA concentrations in tears with a maximal concentration of 94 microg ml(-1) over the observation period. This study demonstrated that the prodrug solution was well tolerated and that clinically significant CsA tear concentrations were achieved. UNIL088 is a promising molecule in the treatment of immune-related disorders of the eye.

Mots-clés
  • Administration, Topical
  • Animals
  • Cyclosporine/administration & dosage/pharmacokinetics/toxicity
  • Drug Tolerance
  • Eye/drug effects
  • Immunosuppressive Agents/pharmacokinetics
  • Male
  • Prodrugs/administration & dosage/pharmacokinetics/toxicity
  • Rabbits
  • Tears/metabolism
Citation (format ISO)
LALLEMAND, Frédéric et al. A novel water-soluble cyclosporine A prodrug: ocular tolerance and in vivo kinetics. In: International journal of pharmaceutics, 2005, vol. 295, n° 1-2, p. 7–14. doi: 10.1016/j.ijpharm.2004.12.015
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Article (Published version)
accessLevelRestricted
Identifiants
ISSN du journal0378-5173
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Création05/07/2016 08:32:00
Première validation05/07/2016 08:32:00
Heure de mise à jour15/03/2023 00:31:39
Changement de statut15/03/2023 00:31:38
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